Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction.
OBJECTIVE
Results from clinical trials suggest that cardiac function after acute myocardial infarction (AMI) can be enhanced by an intracoronary infusion of autologous unselected nucleated bone marrow cells (BMCs). Release of paracrine factors has been proposed as a mechanism for these therapeutic effects; however, this hypothesis has not been tested in humans.


RESULTS
BMCs and peripheral blood leucocytes (PBLs) were obtained from 15 patients with AMI and cultured in serum-free medium to obtain conditioned supernatants (SN). BMC-SN stimulated human coronary artery endothelial cell proliferation, migration, and tube formation, and induced cell sprouting in a mouse aortic ring assay. Moreover, BMC-SN protected rat cardiomyocytes from cell death induced by simulated ischaemia or ischaemia followed by reperfusion. While PBL-SN promoted similar effects on endothelial cells and cardiomyocytes, BMC-SN and PBL-SN in combination promoted synergistic effects. As shown by ProteinChip and GeneChip array analyses (each performed in triplicate), BMCs and PBLs expressed distinct patterns of pro-angiogenic and cytoprotective secreted factors.


CONCLUSIONS
Our data support the paracrine hypothesis and suggest that characterization of the BMC secretome may lead to an identification of factors with therapeutic potential after AMI.
Korf-Klingebiel
Mortimer
M
Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Kempf
Tibor
T
Sauer
Thomas
T
Brinkmann
Eva
E
Fischer
Philipp
P
Meyer
Gerd P
GP
Ganser
Arnold
A
Drexler
Helmut
H
Wollert
Kai C
KC
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000379:methods*; D003331:Coronary Vessels / Q000502:physiology / Q000601:surgery*; D016207:Cytokines / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism; D016896:Treatment Outcome
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins